The Genetic Epidemiology Research Branch at the National Institute of Mental Health (NIMH) has partnered with U PENN and CHOP in the design and assessments, as well as the data analysis of this rich resource. The NIMH team has particularly focused on the topics of medical-mental comorbidity, mood disorders, and migraine and other neurologic conditions. Our publication on physical-mental comorbidity (Merikangas et al, 2015) revealed that there was a direct association between the severity of physical conditions and most classes of mental disorders, as well as with functional impairment. We also found that there was specificity of associations between mood disorders with immune/inflammatory conditions, and between behavior disorders and attention deficit hyperactivity disorder with neurologic/central nervous system conditions. Findings demonstrate the strong overlap between physical and mental conditions and its impact on severity and functional impairment in youth. In our analyses of racial-ethnic disparities in sub-threshold psychosis symptoms (Paksarian et al, under review), we found that ethnic minority youth were more likely to manifest sub-threshold psychosis symptoms than were non-Hispanic white youth. However, there was some indication that these associations differed between minority groups and were strongest for non-Hispanic black youth. We have also completed analyses of comorbidity patterns of migraine with other physical and mental conditions that showed specific associations between migraine with anxiety and depressive disorders in youth (Lateef et al, under review). Additionally, we have continued to work with collaborators at Harvard to examine the heritability of behavioral phenotypes in the study (Robinson et al, 2015). This work showed that several components of childhood cognitive abilities, such as reading ability, emotion identification, and verbal memory, are influenced by genetics. These findings further support the need to study the diverse cognitive abilities of children and contribute greatly to the existing research on the subject. Our collaborative efforts have also yielded 2 methodological publications in the past year: 1) a manuscript describing the methodology of the study of youth at risk for psychotic spectrum symptoms (Calkins et al, 2014) and 2) a manuscript providing an overview of PNC recruitment and clinical assessment methods to allow informed use and interpretation of the PNC resource by the scientific community (Calkins et al, 2015). Public Health Impact: This report on physical and mental comorbidity is the first study to investigate the specificity of associations between a broad range of physical and mental conditions using a large, systematically obtained pediatric sample with enriched information from electronic medical records and direct interviews. The findings highlight the importance of capturing the roots of both physical and mental disorders in childhood in order to trace their evolution into chronic diseases causing major public health concerns. Information generated from such a sample may have profound impact on the current clinical practices. Our research on race-ethnicity and psychosis is one of the few studies to document racial-ethnic disparities in sub-threshold psychosis symptoms among U.S. youth, and adds to a growing amount of literature on racial and ethnic health disparities that document the disproportionate health burden of the minorities in the U.S. The study on migraine comorbidity indicates that comorbidity could be an important source of the clinical and etiologic heterogeneity in migraine. Future Plans: The NIMH team will continue to work with the U PENN and CHOP collaborators to conceptualize and analyze the data, prepare manuscripts for publication, and facilitate follow-up of the subsample with mood disorders. The NIMH team will focus analytic effort on 1) using the geographic information system data to examine associations between area-level measures, such as neighborhood socioeconomic deprivation, and mood and other mental disorders; 2) using latent class analysis approach in qualitative phenotype identification; 3) conducting genome-wide complex trait analysis on selected disorders and patterns of disorders in youth; 4) examining the patterns of medical-psychiatric comorbidity in more depth; and 5) defining dimensional measures of psychopathology in the dataset. In addition, the NIMH will continue to collaborate with U PENN to follow-up youth with mood symptoms and disorders to complement the ongoing follow-up of youth at risk for psychosis in order to supplement the clinical and biomarkers research on mood disorder subtypes now underway in the NIMH Family Study of Affective Spectrum Disorders.